In 1973, we discovered that upon virus-induced malignant transformation, fibroblasts lost an antigenic entity (fibroblast surface antigen). The antigen appeared to be comprised of two high molecular weight polypeptides and was present in circulating plasma. We have established identity between the high molecular weight glycoprotein component (SF210, fibronectin), the LETS protein and "cold-insoluble globulin" and tentatively between the rapidly turning over component (SF145) and gamma 2-macroglobulin. We have reported that fibronectin is synthesized but is not retained on surface of malignantly transformed cells (sarcoma, glioma). We plan to extend our studies 1) on the histological distribution of fibronectin in humans in normal and diseased conditions 2) on which human tumor cell types produce fibronectin and whether fibronectin produced by normal and malignant cells differs in any way in its peptide and carbohydrate portions 3) on eradication of fibroblasts from cultures of normal and malignant epithelial and parenchymal cells using antifibronectin antibodies 4) on our findings on cross-linking of fibronectin by plasma transglutaminase 5) on fibronectin as a ConA receptor possibly restricting membrane fluidity 6) on significance of production of SF145 (gamma 2-macroglobulin) by untransformed cells 7) on involvement of proteases and microfilament functions in mechanism of release of fibronectin. BIBLIOGRAPHIC REFERENCES: Vaheri, A., Ruoslahti, E., Westermark, B., and Ponten, J.: A common cell-type specific surface antigen (SF) in cultured human glial cells and fibroblasts: loss in malignant cells. J. Exp. Med. 143:64-72, 1976. Kuusela, P., Ruoslahti, E., and Vaheri, A.: Polypeptides of a glycoprotein antigen (SF) present in serum and surface of normal but not of transformed chicken fibroblasts. Biochim. Biophys. Acta 379:295-313, 1975.